A wound-induced differentiation trajectory for neurons.

التفاصيل البيبلوغرافية
العنوان: A wound-induced differentiation trajectory for neurons.
المؤلفون: Hulett RE, Gehrke AR, Gompers A, Rivera-López C, Srivastava M
المصدر: BioRxiv : the preprint server for biology [bioRxiv] 2023 May 11. Date of Electronic Publication: 2023 May 11.
نوع المنشور: Preprint
اللغة: English
بيانات الدورية: Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
مستخلص: Animals capable of whole-body regeneration can replace any missing cell type and regenerate fully-functional new organs, de novo . The regeneration of a new brain requires the formation of diverse neuronal cell types and their assembly into an organized structure and correctly-wired circuits. Recent work in various regenerative animals has revealed transcriptional programs required for the differentiation of distinct neuronal subpopulations, however how these transcriptional programs are initiated upon amputation remains unknown. Here, we focused on the highly regenerative acoel worm, Hofstenia miamia , to study wound-induced transcriptional regulatory events that lead to the production of neurons. Footprinting analysis using chromatin accessibility data on an improved genome assembly revealed that binding sites for the NFY transcription factor complex were significantly bound during regeneration, showing a dynamic increase in binding within one hour upon amputation specifically in tail fragments, which will regenerate a new brain. Strikingly, NFY targets were highly enriched for genes with neuronal functional. Single-cell transcriptome analysis combined with functional studies identified sox4 + stem cells as the likely progenitor population for multiple neuronal subtypes. Further, we found that wound-induced sox4 expression is likely under direct transcriptional control by NFY, uncovering a mechanism for how early wound-induced binding of a transcriptional regulator results in the initiation of a neuronal differentiation pathway.
Highlights: A new chromosome-scale assembly for Hofstenia enables comprehensive analysis of transcription factor binding during regeneration NFY motifs become dynamically bound by 1hpa in regenerating tail fragments, particularly in the loci of neural genes A sox4 + neural-specialized stem cell is identified using scRNA-seq sox4 is wound-induced and required for differentiation of multiple neural cell types NFY regulates wound-induced expression of sox4 during regeneration.
التعليقات: Update in: Proc Natl Acad Sci U S A. 2024 Jul 16;121(29):e2322864121. doi: 10.1073/pnas.2322864121. (PMID: 38976727)
معلومات مُعتمدة: R35 GM128817 United States GM NIGMS NIH HHS
تواريخ الأحداث: Date Created: 20230522 Latest Revision: 20240729
رمز التحديث: 20240729
مُعرف محوري في PubMed: PMC10197691
DOI: 10.1101/2023.05.10.540286
PMID: 37214981
قاعدة البيانات: MEDLINE
الوصف
تدمد:2692-8205
DOI:10.1101/2023.05.10.540286